Interest in Genomic Medicine Research for Heart Disease Continues to Grow

This is the third part of an interview with Faraz Ali, MBA. For the first part, click here and for the second part click here.

Faraz Ali, MBA

Heart disease remains the leading cause of death in the world, and as such both companies and academic institutions have maintained a strong interest in developing novel treatments for such indications. A growing modality of interest in cardiology is genomic medicine, which includes approaches such as gene transfer, gene silencing, and gene-editing.

CGTLive® recently spoke with Faraz Ali, MBA, the chief executive officer of Tenaya Therapeutics, a company developing gene transfer and gene-editing approaches for cardiovascular indications, at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. In the interview, Ali spoke about the growing interest in such approaches in cardiology research and their potential to eventually treat very prevalent forms of heart disease.

CGTLive: Can you talk a little bit about trends in research for cardiovascular medicine?

Faraz Ali, MBA: Heart disease remains the leading cause of death in the world, more than all of oncology combined. We've said for a long time as a company that heart disease is going to go the direction of oncology, which means we're going to take large indications and begin to slice them into smaller subpopulations based on genetics or other factors. That is indeed how things are playing out with some initial work in transthyretin amyloidosis (ATTR) cardiomyopathy (CM) and arrhythmogenic CM, but now it's going broader than that. We just see that we're still at the beginning of a very exciting inflection point in precision medicine for heart disease, where more genetic insight into the genetic drivers of heart disease, combined with more genetic tools, just enables a lot.

We have examples out there of this: Intellia has a gene-editing program that's actually directed to the liver that helps to address ATTR-CM and they've had some positive data; Rocket Pharmaceuticals, our friends and peers, have shown some really promising data with Danon disease with a gene transfer approach using adeno-associated virus serotype 9 (the same capsid that we're using for our lead gene therapy program so it provides good validation), showing that over many years a 1-time dose expressing the missing protein has led to heart reduction over time. That's a great comp for us to show that this is possible and so that gives us hope.

With our work, we are in the clinic now, and we're going to generate data on TN-201 in the second half of this year and we're excited for that. Then we're going to start dosing patients with TN-401 in our genetic arrhythmia program.

I think the whole field is at an inflection point where there's now us as well as multiple other companies going after genetic forms of heart disease with either gene transfer or gene-editing. There's been advances in capsid engineering—just unlocking more and more things—and more and more people are interested in it. Back when we started, there weren't a lot. But every time we come here, we see a few more people [and find ourselves saying] like “okay, they seem to be doing something that sounds pretty familiar.” I guess imitation is maybe the best form of flattery. But there's a lot of opportunity, there's a lot of unmet need, and we have better tools than ever to do something really meaningful for the lives of patients. That's what gets us all up at Tenaya in the morning. We've got a good contingent over here and that keeps us doing the work that we do.

So I think the initial horizon is in these rare genetic CMs—but I think with the platform enhancements and the better genetic insight also into prevalent forms of heart disease, and with breakthroughs in platform technologies, like better capsids and better manufacturing—all this work we're doing in genetic forms of heart disease is opening up the potential for going after larger indications as well—like heart failure (HF) with reduced ejection fraction or HF with preserved ejection fraction—and going after genetic variants. As long as we can have capsids that have a profile that allows us to go after larger indications and manufacturing platforms that can really allow us to scale up way past 1,000 and 2,000 liters and get to much higher scales that can allow us to go down to lower cost of goods—that's where the puck is going. That's what's really exciting.

We're putting one step in front of another, and every year get excited by where the field is going and what more is possible. But the end goal is addressing the leading cause of death in the world with a variety of approaches—gene silencing, gene transfer, gene-editing, [etc.] We're a modality agnostic company. Because we're at ASGCT I'm talking primarily about genetic medicines, but in addition to genetic medicines we also have nongenetic medicines: we have a clinical stage program for a small molecule for a large indication. We're cardio specialists and we're excited by everything that's happening in heart disease, but we're particularly excited about what's happening in genetic CMs because I think it's going to open up a lot.

This transcript has been edited for clarity.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.